Preoperative Hypofractionated Radiotherapy With FOLFOX for Esophageal or Gastroesophageal Junction Adenocarcinoma

NCT ID: NCT06078709

Last Updated: 2025-09-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

99 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-11-20

Study Completion Date

2026-11-30

Brief Summary

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This phase II trial tests how well preoperative (prior to surgery) radiation therapy with fluorouracil, oxaliplatin, and leucovorin calcium (FOLFOX) works for the treatment of stage I-III esophageal or gastroesophageal junction adenocarcinoma. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Fluorouracil stops cells from making deoxyribonucleic acid (DNA) and it may kill tumor cells. Leucovorin is not a chemotherapy medication but is given in conjunction with chemotherapy. Leucovorin is used with the chemotherapy medication fluorouracil to enhance the effects of the fluorouracil, in other words, to make the drug work better. Oxaliplatin is in a class of medications called platinum-containing antineoplastic agents. It damages the cell's DNA and may kill tumor cells. Giving preoperative hypofractionated radiation with fluorouracil and oxaliplatin may kill more tumor cells in patients with stage I-III esophageal or gastroesophageal junction adenocarcinoma.

Detailed Description

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PRIMARY OBJECTIVE:

I. To demonstrate non-inferiority of pathologic complete response (pCR) with hypofractionated radiotherapy and concurrent FOLFOX compared to historical controls.

SECONDARY OBJECTIVES:

I. Report targeted acute grade ≥ 3 gastrointestinal (GI) toxicity, per Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.

II. Assess post-operative toxicity for patients undergoing esophagectomy, as determined by the Clavien-Dindo Classification.

III. Analyze patient-reported quality of life, per Functional Assessment of Cancer Therapy- Esophageal (FACT-E).

IV. Determine the financial toxicity of hypofractionated radiotherapy, using Comprehensive Score for Financial Toxicity (COST-FACIT).

V. Report overall survival and progression-free survival. VI. Report long-term toxicity secondary to trimodality therapy. VII. Report event-free survival. VIII. Assess outcomes for patients treated with hypofractionated radiotherapy and FOLFOX but who did not proceed to esophagectomy.

IX. Compare toxicity of chemoradiation between patients receiving proton based versus (vs.) photon-based radiotherapy.

X. Compare clinical outcomes and pCR for patients receiving hypofractioned radiotherapy but different induction chemo (immuno) therapy regimens: no induction vs. fluorouracil, oxaliplatin, leucovorin, docetaxel (FLOT) vs. FLOT + durvalumab.

CORRELATIVE OBJECTIVES:

I. Explore the predictive and prognostic role for circulating tumor DNA in esophageal cancer.

II. Study the utility of whole exome and germline sequencing to predict chemoradiation treatment response.

III. Explore the predictive power of whole exome sequencing regarding chemoradiotherapy toxicity.

IV. Implement whole exome and germline sequencing to personalize immunotherapy in esophageal cancer.

V. Study the predictive and prognostic role of tumor-derived extracellular vesicles in esophageal cancer.

OUTLINE:

INDUCTION CHEMOTHERAPY: Patients receive 5-FU intravenously (IV) over 24 hours on day 1, leucovorin calcium IV over 10-120 minutes on day 1, oxaliplatin IV over 2-6 hours on day 1, and docetaxel IV over 1 hour on day 1 of each cycle. Treatment repeats every 2 weeks for a total of up to 6 cycles in the absence of disease progression or unacceptable toxicity. Eligible patients also receive durvalumab IV over 1 hour every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of FLOT, patients undergo radiation therapy daily for 3 weeks with 2 concurrent cycles of FOLFOX.

FOLFOX: Patients receive oxaliplatin IV over 2-6 hours on day 1, leucovorin calcium IV over 10-120 minutes on day 1, and and fluorouracil IV over 46-48 hours on days 1 and 2. of each cycle. Treatment repeats every 2 weeks for a total of 3 cycles in the absence of disease progression or unacceptable toxicity. Starting at cycle 2, patients undergo radiation therapy daily on Monday through Friday for a total of 15 treatments. Patients undergo esophagogastroduodenoscopy (EGD) and/or endoscopic ultrasound (EUS) during screening and undergo computed tomography (CT)/position emission tomography (PET) scan and CT scan as well as blood and tissue sample collection throughout the study.

After completion of study treatment, patients are followed up at 6,12 and 24 months and then up to 5 years.

Conditions

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Clinical Stage I Esophageal Adenocarcinoma AJCC v8 Clinical Stage I Gastroesophageal Junction Adenocarcinoma AJCC v8 Clinical Stage II Esophageal Adenocarcinoma AJCC v8 Clinical Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8 Clinical Stage III Esophageal Adenocarcinoma AJCC v8 Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (FLOT and Radiation and FOLFOX)

Patients received Induction Chemotherapy \[FLOT (5-FU/leucovorin/oxaliplatin/docetaxel)\] following by radiation therapy daily for 3 weeks with 2 concurrent cycles of FOLFOX per protocol. See detailed description for more information.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Computed Tomography

Intervention Type PROCEDURE

Undergo CT and PET/CT scan

Endoscopic Ultrasound

Intervention Type PROCEDURE

Undergo EUS

Esophagogastroduodenoscopy

Intervention Type PROCEDURE

Undergo EGD

Fluorouracil

Intervention Type DRUG

Given IV

Hypofractionated Radiation Therapy

Intervention Type RADIATION

Undergo hypofractionated radiation therapy

Leucovorin Calcium

Intervention Type DRUG

Given IV

Oxaliplatin

Intervention Type DRUG

Given IV

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET and PET/CT scan

Survey Administration

Intervention Type OTHER

Ancillary studies

Docetaxel

Intervention Type DRUG

Given IV

Durvalumab

Intervention Type BIOLOGICAL

Given IV

Interventions

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Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Computed Tomography

Undergo CT and PET/CT scan

Intervention Type PROCEDURE

Endoscopic Ultrasound

Undergo EUS

Intervention Type PROCEDURE

Esophagogastroduodenoscopy

Undergo EGD

Intervention Type PROCEDURE

Fluorouracil

Given IV

Intervention Type DRUG

Hypofractionated Radiation Therapy

Undergo hypofractionated radiation therapy

Intervention Type RADIATION

Leucovorin Calcium

Given IV

Intervention Type DRUG

Oxaliplatin

Given IV

Intervention Type DRUG

Positron Emission Tomography

Undergo PET and PET/CT scan

Intervention Type PROCEDURE

Survey Administration

Ancillary studies

Intervention Type OTHER

Docetaxel

Given IV

Intervention Type DRUG

Durvalumab

Given IV

Intervention Type BIOLOGICAL

Other Intervention Names

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Biological Sample Collection Biospecimen Collected Specimen Collection CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography CT CT Scan tomography Computerized Tomography (CT) scan endosonography EUS EGD Upper Endoscopy 5 Fluorouracil 5 Fluorouracilum 5 FU 5-Fluoro-2,4(1H, 3H)-pyrimidinedione 5-Fluorouracil 5-Fluracil 5-Fu 5FU AccuSite Carac Fluoro Uracil Fluouracil Flurablastin Fluracedyl Fluracil Fluril Fluroblastin Ribofluor Ro 2-9757 Ro-2-9757 2,4-Dioxo-5-fluoropyrimidine 51-21-8 Hypofractionated Hypofractionated Radiotherapy hypofractionation Radiation, Hypofractionated Adinepar Calcifolin Calcium (6S)-Folinate Calcium Folinate Calcium Leucovorin Calfolex Calinat Cehafolin Citofolin Citrec Citrovorum Factor Cromatonbic Folinico Dalisol Disintox Divical Ecofol Emovis Factor, Citrovorum Flynoken A Folaren Folaxin FOLI-cell Foliben Folidan Folidar Folinac Folinate Calcium folinic acid Folinic Acid Calcium Salt Pentahydrate Folinoral Folinvit Foliplus Folix Imo Lederfolat Lederfolin Leucosar leucovorin Rescufolin Rescuvolin Tonofolin Wellcovorin 1-OHP Ai Heng Aiheng Dacotin Dacplat Diaminocyclohexane Oxalatoplatinum Eloxatin Eloxatine JM-83 Oxalatoplatin Oxalatoplatinum RP 54780 RP-54780 SR-96669 JM83 RP54780 SR96669 Medical Imaging PET PET Scan Positron emission tomography (procedure) Positron Emission Tomography Scan Positron-Emission Tomography proton magnetic resonance spectroscopic imaging PT 148408-66-6 Docecad N-Debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol RP 56976 RP-56976 RP56976 Taxotere Imfinzi MEDI 4736 MEDI-4736 MEDI4736 Disulfide with Human Monoclonal MEDI4736 Kappa-chain Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain) Immunoglobulin G1

Eligibility Criteria

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Inclusion Criteria

* Age ≥ 18 years
* Histological confirmation of esophageal or gastroesophageal junction adenocarcinoma, American Joint Committee on Cancer (AJCC) 8th edition stage T1-4N0-3M0
* Candidate for trimodality therapy: neoadjuvant chemo (immuno) therapy, chemoradiation, and esophagectomy
* Surgical consultation has confirmed that patient is an appropriate candidate for esophagectomy
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
* Negative pregnancy test done ≤ 7 days prior to chemotherapy, for women of childbearing potential only
* Ability to provide written informed consent and complete questionnaire(s) by themselves or with assistance
* Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
* Willing to provide blood and tissue samples for correlative research purposes

Exclusion Criteria

* Clinical or biopsy-proven distant metastatic disease (AJCC 8th edition stage TanyNanyM1)
* Cervical or upper esophageal tumor
* Prior chemotherapy or radiotherapy for esophageal cancer or history of radiotherapy to the thorax
* Co-morbid systemic illnesses or other severe concurrent disease which, in the judgement of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with proper assessment of adverse events
* Receiving any investigational agent which would be considered as a treatment for the primary neoplasm or other active malignancy ≤ 1 year prior to registration that is considered by the investigator to interfere with the current treatment or measurement of outcomes
* Any of the following:

* Pregnant women
* Nursing women
* Men or women of childbearing potential who are unwilling to employ adequate contraception
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mayo Clinic

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Christopher L. Hallemeier, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic in Rochester

Locations

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Mayo Clinic in Arizona

Scottsdale, Arizona, United States

Site Status NOT_YET_RECRUITING

Mayo Clinic in Florida

Jacksonville, Florida, United States

Site Status ACTIVE_NOT_RECRUITING

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Clinical Trials Referral Office

Role: CONTACT

855-776-0015

Facility Contacts

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Clinical Trials Referral Office

Role: primary

855-776-0015

Clinical Trials Referral Office

Role: primary

855-776-0015

Related Links

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Other Identifiers

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NCI-2023-07432

Identifier Type: REGISTRY

Identifier Source: secondary_id

GMROR2241

Identifier Type: OTHER

Identifier Source: secondary_id

23-001689

Identifier Type: OTHER

Identifier Source: secondary_id

GMROR2241

Identifier Type: -

Identifier Source: org_study_id

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